title: Tunable signal processing through a kinase control cycle: the IKK signaling node.
abstract: The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a regulatory cycle comprising a poised, an active, and an inactive state. We hypothesize that it operates as a modulator of signal dynamics, actively reshaping the signals generated at the receptor proximal level. Here we show that a regulatory cycle can function in at least three dynamical regimes, tunable by regulating a single kinetic parameter. In particular, the simplest three-state regulatory cycle can generate signals with two well-defined phases, each with distinct coding capabilities in terms of the information they can carry about the stimulus. We also demonstrate that such a kinase cycle can function as a signal categorizer classifying diverse incoming signals into outputs with a limited set of temporal activity profiles. Finally, we discuss the extension of the results to other regulatory motifs that could be understood in terms of the regimes of the three-state cycle.
authors.affiliation: Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Behar
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoffmann
mesh_terms: D004789:Enzyme Activation; D051550:I-kappa B Kinase / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D051550:I-kappa B Kinase